Actin-specific ADP-ribosyltransferase Produced by a Clostridium Difficile Strain

Overview

Journal Infect Immun

Publisher American Society for Microbiology

Specialty Allergy & Immunology

Date 1988 Sep 1

PMID 3137166

Citations 117

Authors

M R Popoff

E J Rubin

D M Gill

P Boquet

Affiliations

Soon will be listed here.

Abstract

By screening possible ADP-ribosyltransferase activities in culture supernatants from various Clostridium species, we have found one Clostridium difficile strain (CD196) (isolated in our laboratory) that is able to produce, in addition to toxins A and B, a new ADP-ribosyltransferase that was shown to covalently modify cell actin as Clostridium botulinum C2 or Clostridium perfringens E iota toxins do. The molecular weight of the CD196 ADP-ribosyltransferase (CDT) was determined to be 43 kilodaltons, and its isoelectric point was 7.8. No cytotoxic activity on Vero cells or lethal activity upon injection in mice was associated with this enzyme. CDT was neither related to C. difficile A or B toxins nor to C. botulinum C2 toxin component I. However, Vero cells cultivated in the presence of C. difficile B toxin had a lower amount of actin able to be ADP-ribosylated by CDT or C2 toxin in vitro. Antibodies raised against CDT reacted by immunoblot analysis with a 43-kilodalton protein of C. perfringens type E culture supernatant producing the iota toxin.

Citing Articles

Antibiotic-Associated Diarrhea Beyond : A Scoping Review.

Selvaraj V, Alsamman M Brown J Hosp Med. 2025; 2(1):39745.

PMID: 40046540 PMC: 11878822. DOI: 10.56305/001c.39745.

The N-terminus of the transferase A component directs toxin activity and potency.

Mullard R, Sheedlo M mBio. 2024; 16(1):e0240524.

PMID: 39611841 PMC: 11708034. DOI: 10.1128/mbio.02405-24.

General ADP-Ribosylation Mechanism Based on the Structure of ADP-Ribosyltransferase-Substrate Complexes.

Tsuge H, Habuka N, Yoshida T Toxins (Basel). 2024; 16(7).

PMID: 39057953 PMC: 11281641. DOI: 10.3390/toxins16070313.

Exploring the Toxin-Mediated Mechanisms in Infection.

Pourliotopoulou E, Karampatakis T, Kachrimanidou M Microorganisms. 2024; 12(5).

PMID: 38792835 PMC: 11124097. DOI: 10.3390/microorganisms12051004.

infection: history, epidemiology, risk factors, prevention, clinical manifestations, treatment, and future options.

Di Bella S, Sanson G, Monticelli J, Zerbato V, Principe L, Giuffre M Clin Microbiol Rev. 2024; 37(2):e0013523.

PMID: 38421181 PMC: 11324037. DOI: 10.1128/cmr.00135-23.

References

Morrissey J . Silver stain for proteins in polyacrylamide gels: a modified procedure with enhanced uniform sensitivity. Anal Biochem. 1981; 117(2):307-10. DOI: 10.1016/0003-2697(81)90783-1. View

Burnette W . "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate--polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem. 1981; 112(2):195-203. DOI: 10.1016/0003-2697(81)90281-5. View

SULLIVAN N, Pellett S, Wilkins T . Purification and characterization of toxins A and B of Clostridium difficile. Infect Immun. 1982; 35(3):1032-40. PMC: 351151. DOI: 10.1128/iai.35.3.1032-1040.1982. View

Donta S, Sullivan N, Wilkins T . Differential effects of Clostridium difficile toxins on tissue-cultured cells. J Clin Microbiol. 1982; 15(6):1157-8. PMC: 272271. DOI: 10.1128/jcm.15.6.1157-1158.1982. View

OHISHI I . Response of mouse intestinal loop to botulinum C2 toxin: enterotoxic activity induced by cooperation of nonlinked protein components. Infect Immun. 1983; 40(2):691-5. PMC: 264910. DOI: 10.1128/iai.40.2.691-695.1983. View

Borriello S, Carman R . Association of iota-like toxin and Clostridium spiroforme with both spontaneous and antibiotic-associated diarrhea and colitis in rabbits. J Clin Microbiol. 1983; 17(3):414-8. PMC: 272657. DOI: 10.1128/jcm.17.3.414-418.1983. View

Carlsson L, Lazarides E . ADP-ribosylation of the Mr 83,000 stress-inducible and glucose-regulated protein in avian and mammalian cells: modulation by heat shock and glucose starvation. Proc Natl Acad Sci U S A. 1983; 80(15):4664-8. PMC: 384104. DOI: 10.1073/pnas.80.15.4664. View

Simpson L . Molecular basis for the pharmacological actions of Clostridium botulinum type C2 toxin. J Pharmacol Exp Ther. 1984; 230(3):665-9. View

Roa M, Boquet P . Interaction of tetanus toxin with lipid vesicles at low pH. Protection of specific polypeptides against proteolysis. J Biol Chem. 1985; 260(11):6827-35. View

10.

Pothoulakis C, Barone L, Ely R, Faris B, Clark M, Franzblau C . Purification and properties of Clostridium difficile cytotoxin B. J Biol Chem. 1986; 261(3):1316-21. View

11.

OHISHI I, Tsuyama S . ADP-ribosylation of nonmuscle actin with component I of C2 toxin. Biochem Biophys Res Commun. 1986; 136(2):802-6. DOI: 10.1016/0006-291x(86)90511-5. View

12.

Simpson L . Molecular pharmacology of botulinum toxin and tetanus toxin. Annu Rev Pharmacol Toxicol. 1986; 26:427-53. DOI: 10.1146/annurev.pa.26.040186.002235. View

13.

Aktories K, Barmann M, OHISHI I, Tsuyama S, Jakobs K, Habermann E . Botulinum C2 toxin ADP-ribosylates actin. Nature. 1986; 322(6077):390-2. DOI: 10.1038/322390a0. View

14.

Florin I, Thelestam M . ADP-ribosylation in cultured cells treated with Clostridium difficile toxin B. Biochem Biophys Res Commun. 1986; 139(1):64-70. DOI: 10.1016/s0006-291x(86)80080-8. View

15.

Robertson D, Leppla S . Molecular cloning and expression in Escherichia coli of the lethal factor gene of Bacillus anthracis. Gene. 1986; 44(1):71-8. DOI: 10.1016/0378-1119(86)90044-2. View

16.

Stiles B, Wilkins T . Clostridium perfringens iota toxin: synergism between two proteins. Toxicon. 1986; 24(8):767-73. DOI: 10.1016/0041-0101(86)90101-7. View

17.

Stiles B, Wilkins T . Purification and characterization of Clostridium perfringens iota toxin: dependence on two nonlinked proteins for biological activity. Infect Immun. 1986; 54(3):683-8. PMC: 260223. DOI: 10.1128/iai.54.3.683-688.1986. View

18.

Simpson L, Stiles B, Zepeda H, Wilkins T . Molecular basis for the pathological actions of Clostridium perfringens iota toxin. Infect Immun. 1987; 55(1):118-22. PMC: 260288. DOI: 10.1128/iai.55.1.118-122.1987. View

19.

Popoff M . Purification and characterization of Clostridium sordellii lethal toxin and cross-reactivity with Clostridium difficile cytotoxin. Infect Immun. 1987; 55(1):35-43. PMC: 260277. DOI: 10.1128/iai.55.1.35-43.1987. View

20.

Reuner K, Presek P, Boschek C, Aktories K . Botulinum C2 toxin ADP-ribosylates actin and disorganizes the microfilament network in intact cells. Eur J Cell Biol. 1987; 43(1):134-40. View